The hypotheses to be tested in each case have been organized according to the following three Specific Aims. Specific Aim #1: To investigate the potential for endothelial cell (EC) mitogens to accelerate re-endothelialization (rET); Specific Aim #2: To investigate certain mechanisms by which EC mitogens facilitate rET; and Specific Aim #3: To investigate augmented rET using EC precursors isolated from peripheral blood. The studies will be performed in vitro and in vivo. The latter will include a hyperlipidemic rabbit model of double-balloon injury, and, in selected cases, rat and mouse models of single and/or double-balloon injury. Experiments in Specific Aim #1 are expected to define, short of human studies, the potential for EC mitogens to effectively modulate pathologic alteration of the artery wall. Experiments from Specific Aim #2 are expected to elucidate the role of vascular endothelial growth factor (VEGF) as a previously unappreciated endogenous regulatory factor responsible for maintaining and restoring the integrity of the vascular endothelium. Experiments form Specific Aim 3 are considered by the applicant to constitute a "supply side" strategy that will consider circulating EC precursors as penultimate ECs that may be used in conjunction with EC mitogens to augment rET.